scholarly journals Mechanisms of Berberine for the Treatment of Atherosclerosis Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Xuejiao Xie ◽  
Xingyu Ma ◽  
Siyu Zeng ◽  
Wansi Tang ◽  
Liucheng Xiao ◽  
...  

Atherosclerosis is a common metabolic disease characterized by lipid metabolic disorder. The processes of atherosclerosis include endothelial dysfunction, new endothelial layer formation, lipid sediment, foam cell formation, plaque formation, and plaque burst. Owing to the adverse effects of first-line medications, it is urgent to discover new medications to deal with atherosclerosis. Berberine is one of the most promising natural products derived from traditional Chinese medicine. However, the panoramic mechanism of berberine against atherosclerosis has not been discovered clearly. In this study, we used network pharmacology to investigate the interaction between berberine and atherosclerosis. We identified potential targets related to berberine and atherosclerosis from several databases. A total of 31 and 331 putative targets for berberine and atherosclerosis were identified, respectively. Then, we constructed berberine and atherosclerosis targets with PPI data. Berberine targets network with PPI data had 3204 nodes and 79437 edges. Atherosclerosis targets network with PPI data had 5451 nodes and 130891 edges. Furthermore, we merged the two PPI networks and obtained the core PPI network from the merged PPI network. The core PPI network had 132 nodes and 3339 edges. At last, we performed functional enrichment analyses including GO and KEGG pathway analysis in David database. GO analysis indicated that the biological processes were correlated with G1/S transition of mitotic cells cycle. KEGG pathway analysis found that the pathways directly associated with berberine against atherosclerosis were cell cycle, ubiquitin mediated proteolysis, MAPK signaling pathway, and PI3K-Akt signaling pathway. After combining the results in context with the available treatments for atherosclerosis, we considered that berberine inhibited inflammation and cell proliferation in the treatment of atherosclerosis. Our study provided a valid theoretical foundation for future research.

2021 ◽  
Author(s):  
Haiyu Zhang ◽  
Xuedong An ◽  
De Jin ◽  
Jiaxing Tian ◽  
Wenke Liu ◽  
...  

Abstract BackgroundPrevious studies have indicated that the JTTZ formula exhibits clinical benefit in T2D with obesity and hyperlipidemia such as lowering blood glucose, blood lipids, weight, and ameliorating symptoms as well as regulating islet function. However, their mechanism of action remains unclear. T2D with obesity and hyperlipidemia is associated with a severely poor management duo to difficulty in achieving the clinical goals and lack of effective multi-targeted therapies. In this study, we explored its potential mechanisms and therapeutic targets by network pharmacology. MethodsThe active ingredients and targets of JTTZ were obtained in the TCMSP, TCMID, TCM Database@Taiwan, PubChem and Swiss Target Prediction. And the therapeutic targets were searched from TTD, DrugBank Database and DisGeNET. Then, topology analysis were used as secondary screens to identify key hubs of the network. Finally, the data was integrated by Cytoscape software to construct a common network module. PPI networks were visualized to identify the interaction of the candidate targets. GO and KEGG pathway analysis were implemented. Rerult: 110 active compounds and 166 candidate targets of JTTZ against T2D with obesity and hyperlipidemia were obtained to construct compound-targets network. And, the therapeutic targets AKT2, RELA, NFKB1 and GSK3B were identified. GO and KEGG pathway analysis indicated that the biological processes related to inflammatory response, insulin secretion, steroid and bile acid metabolism, and 13 pathways mainly including adipocytokine signaling pathway, cAMP signaling pathway and cGMP-PKG signaling pathway were enriched. ConclusionOur data established that JTTZ intervenes with adipose tissue dysfunction via regulating to the adipocytokine (leptin and adiponectin), AMPK signaling pathway, cAMP and cGMP-PKG signaling pathway, inhibits systematic inflammatory response by NF-κB and MAPK signaling pathway, and ameliorates insulin resistance through PI3K/AKT2 pathway, all of which could thus offer a promising therapeutic strategy. In addition, AKT2, RELA, NFKB1 and GSK3B were identified to be regarded as potential therapeutic targets as well.


2019 ◽  
Author(s):  
Yanyan Tang ◽  
Ping Zhang

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumor in digestive system. CircRNAs involve in lots of biological processes through interacting with miRNAs and their targeted mRNA. We obtained the circRNA gene expression profiles from Gene Expression Omnibus (GEO) and identified differentially expressed genes (DEGs) between PDAC samples and paracancerous tissues. Bioinformatics analyses, including GO analysis, KEGG pathway analysis and PPI network analysis, were conducted for further investigation. We also constructed circRNA‑microRNA-mRNA co-expression network. A total 291 differentially expressed circRNAs were screened out. The GO enrichment analysis revealed that up-regulated DEGs were mainly involved metabolic process, biological regulation, and gene expression, and down-regulated DEGs were involved in cell communication, single-organism process, and signal transduction. The KEGG pathway analysis, the upregulated circRNAs were enriched cGMP-PKG signaling pathway, and HTLV-I infection, while the downregulated circRNAs were enriched in protein processing in endoplasmic reticulum, insulin signaling pathway, regulation of actin cytoskeleton, etc. Four genes were identified from PPI network as both hub genes and module genes, and their circRNA‑miRNA-mRNA regulatory network also be constructed. Our study indicated possible involvement of dysregulated circRNAs in the development of PDAC and promoted our understanding of the underlying molecular mechanisms.


2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Yixuan Lin ◽  
Chuqiao Shen ◽  
Fanjing Wang ◽  
Zhaohui Fang ◽  
Guoming Shen

Objective. To investigate the potential mechanism of action of Yi-Qi-Huo-Xue-Tong-Luo formula (YQHXTLF) in the treatment of diabetic peripheral neuropathy (DPN). Methods. Network pharmacology and molecular docking techniques were used in this study. Firstly, the active ingredients and the corresponding targets of YQHXTLF were retrieved using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform; subsequently, the targets related to DPN were retrieved using GeneCards, Online Mendelian Inheritance in Man (OMIM), Pharmgkb, Therapeutic Target Database (TTD) and Drugbank databases; the common targets of YQHXTLF and DPN were obtained by Venn diagram; afterwards, the “YQHXTLF Pharmacodynamic Component-DPN Target” regulatory network was visualized using Cytoscape 3.6.1 software, and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the potential targets using R 3.6.3 software. Finally, molecular docking of the main chemical components in the PPI network with the core targets was verified by Autodock Vina software. Results. A total of 86 active ingredients and 229 targets in YQHXTLF were screened, and 81 active ingredients and 110 targets were identified to be closely related to diabetic peripheral neuropathy disease. PPI network mapping identified TP53, MAPK1, JUN, and STAT3 as possible core targets. KEGG pathway analysis showed that these targets are mostly involved in AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, and MAPK signaling pathway. The molecular docking results showed that the main chemical components of YQHXTLF have a stable binding activity to the core pivotal targets. Conclusion. YQHXTLF may act on TP53, MAPK1, JUN, and STAT3 to regulate inflammatory response, apoptosis, or proliferation as a molecular mechanism for the treatment of diabetic peripheral neuropathy, reflecting its multitarget and multipathway action, and providing new ideas to further uncover its pharmacological basis and mechanism of action.


2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Rongchang Liu ◽  
Yan Mao ◽  
Zhengyi Gu ◽  
Jinhua He

Background. Hyssopus cuspidatus Boriss. (Shen Xiang Cao (SXC)), a traditional medicine herb in Xinjiang, has a long history of being used by minorities to treat asthma. However, its active antiasthmatic compounds and underlying mechanism of action are still unknown. The aim of this study was to investigate the bioactive compounds and explore the molecular mechanism of SCX in the treatment of asthma using network pharmacology. Methods. The compounds of SCX were collected by a literature search, and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction were used to predict targets and screen active compounds. Moreover, asthma-related targets were obtained based on DisGeNET, Herb, and GeneCards databases, and a protein-protein interaction (PPI) network was built by the STRING database. Furthermore, the topological analysis of the PPI and SXC-compound-target networks were analyzed and established by Cytoscape software. Finally, the RStudio software package was used for carrying out Gene Ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. AutoDock tools and AutoDock Vina were used to molecularly dock the active compounds and key targets. Results. A total of 8 active compounds and 258 potential targets related to SXC were predicted, and PPI network screened out key targets, including IL-6, JUN, TNF, IL10, and CXCL8. GO enrichment analysis involved cell responses to reactive oxygen species, oxidative stress, chemical stress, etc. In addition, KEGG pathway analysis showed that SXC effectively treated asthma through regulation of mitogen-activated protein kinases (MAPK) signaling pathways, interleukin 17 (IL-17) signaling pathways, toll-like receptor (TLR) signaling pathways, and tumor necrosis factor (TNF) signaling pathways. Conclusion. The preliminary study that was based on multiple compounds, multiple targets, and multiple pathways provides a scientific basis for further elucidating the molecules involved and the underlying antiasthma-related mechanisms of SXC.


2020 ◽  
Author(s):  
Liucheng Xiao ◽  
Zonghuan Li ◽  
Chongyuan Fan ◽  
Chenggong Zhu ◽  
Xingyu Ma ◽  
...  

Abstract Background: Xiao-Xian-Xiong decoction is a useful formula in the treatment of atherosclerosis in traditional Chinese medicine. In this study, we aimed to investigate the function of Xiao-Xian-Xiong decoction in the treatment of atherosclerosis. Methods: In this study, we conducted the method of network pharmacology and molecular docking to discover the mechanism of Xiao-Xian-Xiong decoction against atherosclerosis. Then, we validated the function of Xiao-Xian-Xiong decoction in atherosclerosis in vitro. We investigated the function and mechanism of Xiao-Xian-Xiong decoction in RAW264.7 macrophage-derived foam cells.Results: We identified 213 targets of Xiao-Xian-Xiong decoction and 331 targets of atherosclerosis. The PPI networks of Xiao-Xian-Xiong decoction and atherosclerosis were constructed. Furthermore, the two PPI networks were merged and the core PPI network was obtained. Then, functional enrichment analysis was conducted with GO and KEGG signaling pathway analysis. KEGG analysis indicated Xiao-Xian-Xiong decoction was correlated with ubiquitin mediated proteolysis pathway, PI3K-AKT pathway, MAPK pathway, Notch signaling pathway, and TGF-β signaling pathway. At last, we validated the function of Xiao-Xian-Xiong decoction with atherosclerosis in vitro. Xiao-Xian-Xiong decoction reduced lipid accumulation and promoted the outflow of cholesterol in RAW264.7-derived foam cells. Xiao-Xian-Xiong decoction increased the expression of ABCA1 and ABCG1 protein in foam cells. ABCA1 and ABCG1 were related with regulation of the inflammatory pathway and cell proliferation in atherosclerosis.Conclusions: Combined the mechanism of available treatments of atherosclerosis, we inferred Xiao-Xian-Xiong decoction could alleviate atherosclerosis by inhibiting inflammatory response and cell proliferation.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Huijing Zhu ◽  
Xin Zhu ◽  
Yuhong Liu ◽  
Fusong Jiang ◽  
Miao Chen ◽  
...  

Objective. The aim of this study was to identify the candidate genes in type 2 diabetes mellitus (T2DM) and explore their potential mechanisms. Methods. The gene expression profile GSE26168 was downloaded from the Gene Expression Omnibus (GEO) database. The online tool GEO2R was used to obtain differentially expressed genes (DEGs). Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using Metascape for annotation, visualization, and comprehensive discovery. The protein-protein interaction (PPI) network of DEGs was constructed by using Cytoscape software to find the candidate genes and key pathways. Results. A total of 981 DEGs were found in T2DM, including 301 upregulated genes and 680 downregulated genes. GO analyses from Metascape revealed that DEGs were significantly enriched in cell differentiation, cell adhesion, intracellular signal transduction, and regulation of protein kinase activity. KEGG pathway analysis revealed that DEGs were mainly enriched in the cAMP signaling pathway, Rap1 signaling pathway, regulation of lipolysis in adipocytes, PI3K-Akt signaling pathway, MAPK signaling pathway, and so on. On the basis of the PPI network of the DEGs, the following 6 candidate genes were identified: PIK3R1, RAC1, GNG3, GNAI1, CDC42, and ITGB1. Conclusion. Our data provide a comprehensive bioinformatics analysis of genes, functions, and pathways, which may be related to the pathogenesis of T2DM.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e6036 ◽  
Author(s):  
Xin Gao ◽  
Yinyi Chen ◽  
Mei Chen ◽  
Shunlan Wang ◽  
Xiaohong Wen ◽  
...  

Background Bladder cancer is a malignant tumor in the urinary system with high mortality and recurrence rates. However, the causes and recurrence mechanism of bladder cancer are not fully understood. In this study, we used integrated bioinformatics to screen for key genes associated with the development of bladder cancer and reveal their potential molecular mechanisms. Methods The GSE7476, GSE13507, GSE37815 and GSE65635 expression profiles were downloaded from the Gene Expression Omnibus database, and these datasets contain 304 tissue samples, including 81 normal bladder tissue samples and 223 bladder cancer samples. The RobustRankAggreg (RRA) method was utilized to integrate and analyze the four datasets to obtain integrated differentially expressed genes (DEGs), and the gene ontology (GO) functional annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed. Protein-protein interaction (PPI) network and module analyses were performed using Cytoscape software. The OncoLnc online tool was utilized to analyze the relationship between the expression of hub genes and the prognosis of bladder cancer. Results In total, 343 DEGs, including 111 upregulated and 232 downregulated genes, were identified from the four datasets. GO analysis showed that the upregulated genes were mainly involved in mitotic nuclear division, the spindle and protein binding. The downregulated genes were mainly involved in cell adhesion, extracellular exosomes and calcium ion binding. The top five enriched pathways obtained in the KEGG pathway analysis were focal adhesion (FA), PI3K-Akt signaling pathway, proteoglycans in cancer, extracellular matrix (ECM)-receptor interaction and vascular smooth muscle contraction. The top 10 hub genes identified from the PPI network were vascular endothelial growth factor A (VEGFA), TOP2A, CCNB1, Cell division cycle 20 (CDC20), aurora kinase B, ACTA2, Aurora kinase A, UBE2C, CEP55 and CCNB2. Survival analysis revealed that the expression levels of ACTA2, CCNB1, CDC20 and VEGFA were related to the prognosis of patients with bladder cancer. In addition, a KEGG pathway analysis of the top 2 modules identified from the PPI network revealed that Module 1 mainly involved the cell cycle and oocyte meiosis, while the analysis in Module 2 mainly involved the complement and coagulation cascades, vascular smooth muscle contraction and FA. Conclusions This study identified key genes and pathways in bladder cancer, which will improve our understanding of the molecular mechanisms underlying the development and progression of bladder cancer. These key genes might be potential therapeutic targets and biomarkers for the treatment of bladder cancer.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11203
Author(s):  
Dingyu Chen ◽  
Chao Li ◽  
Yan Zhao ◽  
Jianjiang Zhou ◽  
Qinrong Wang ◽  
...  

Aim Helicobacter pylori cytotoxin-associated protein A (CagA) is an important virulence factor known to induce gastric cancer development. However, the cause and the underlying molecular events of CagA induction remain unclear. Here, we applied integrated bioinformatics to identify the key genes involved in the process of CagA-induced gastric epithelial cell inflammation and can ceration to comprehend the potential molecular mechanisms involved. Materials and Methods AGS cells were transected with pcDNA3.1 and pcDNA3.1::CagA for 24 h. The transfected cells were subjected to transcriptome sequencing to obtain the expressed genes. Differentially expressed genes (DEG) with adjusted P value < 0.05, — logFC —> 2 were screened, and the R package was applied for gene ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The differential gene protein–protein interaction (PPI) network was constructed using the STRING Cytoscape application, which conducted visual analysis to create the key function networks and identify the key genes. Next, the Kaplan–Meier plotter survival analysis tool was employed to analyze the survival of the key genes derived from the PPI network. Further analysis of the key gene expressions in gastric cancer and normal tissues were performed based on The Cancer Genome Atlas (TCGA) database and RT-qPCR verification. Results After transfection of AGS cells, the cell morphology changes in a hummingbird shape and causes the level of CagA phosphorylation to increase. Transcriptomics identified 6882 DEG, of which 4052 were upregulated and 2830 were downregulated, among which q-value < 0.05, FC > 2, and FC under the condition of ≤2. Accordingly, 1062 DEG were screened, of which 594 were upregulated and 468 were downregulated. The DEG participated in a total of 151 biological processes, 56 cell components, and 40 molecular functions. The KEGG pathway analysis revealed that the DEG were involved in 21 pathways. The PPI network analysis revealed three highly interconnected clusters. In addition, 30 DEG with the highest degree were analyzed in the TCGA database. As a result, 12 DEG were found to be highly expressed in gastric cancer, while seven DEG were related to the poor prognosis of gastric cancer. RT-qPCR verification results showed that Helicobacter pylori CagA caused up-regulation of BPTF, caspase3, CDH1, CTNNB1, and POLR2A expression. Conclusion The current comprehensive analysis provides new insights for exploring the effect of CagA in human gastric cancer, which could help us understand the molecular mechanism underlying the occurrence and development of gastric cancer caused by Helicobacter pylori.


2020 ◽  
Author(s):  
Hanchu Xiong ◽  
Zihan Chen ◽  
Wenwen Zheng ◽  
Jing Sun ◽  
Qingshuang Fu ◽  
...  

Abstract Background Breast cancer (BC) is a disease with morbidity ranking the first of women worldwidely. FK506-binding protein (FKBP) family has been demonstrated to possess various functions by interacting with different molecular targets in BC. However, a comprehensive ncRNA-mRNA regulatory axis of FKBP has not yet been reported. Methods FKBP related miRNAs were obtained from miRWalk database. Then, potential lncRNAs, transcription factors as well as mRNAs of screened differentially expressed miRNAs (DE-miRNAs) were analysed by using LncBase v.2, miRGen v3 and miRWalk database. Additionally, differential expression and prognostic analysis of lncRNAs were evaluated using TANRIC database. Next, GO annotation and KEGG pathway analysis were processed using DAVID database. Protein-Protein Interaction (PPI) network was established and hub genes were identified using STRING database. Finally, differential expression and prognostic analysis of hub genes were further conducted using UALCAN and bc-GenExMiner v4.2 database, respectively. Results Eleven DE-miRNAs, consisting of four FKBP4 related DE-miRNAs and seven FKBP5 related DE-miRNAs, were screened. 482 predicted lncRNAs were found for DE-miRNAs. Then, expression and prognostic results of nine of top twenty lncRNAs of BC were significantly identified. LINC00662 and LINC00963 expression were significantly associated with patients’ overall survival (OS). Then, nine potential upstream transcription factors were identified in motifs of DE-miRNAs. 320 target genes were identified for GO annotation and KEGG pathway analysis, which were mainly enriched in cysteine-type endopeptidase activity involved in apoptotic process. Construction and analysis in PPI network showed that RAB7A was selected as a hub gene with the toppest connectivity scores. Differential expression analysis of nine in top ten hub genes of BC were significantly identified. RAB7A and ARRB1 expression were significantly related with BC patients’ OS. Conclusions In current study, we firstly established a predicted FKBP-related ncRNA-mRNA regulatory network, thus exploring a comprehensive interpretation of molecular mechanisms and providing potential clues in seeking novel therapeutics for BC. In the future, much more experiments should be conducted to verify our findings.


2020 ◽  
Author(s):  
Ling Zhang ◽  
Yunkai Dai ◽  
Yuping Li ◽  
Weijing Chen ◽  
Ruliu Li ◽  
...  

Abstract Background Chronic gastritis (CG) is an inflammatory disease which is one of the common diseases of the digestive system. To investigate the mechanisms of herbal pair Acoritataninowii Rhizoma(Shichangpu, AR) and Curcumae Radix༈Yujin, CR༉ in treatment of CG based on the network pharmacology. Methods The possible active ingredients and targets of AR-CR were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The UniProt database was used to query the human gene corresponding to each target protein. The genes related to CG were collected from the GeneCards database, the OMIM database, the DisGeNET database and the PharmGKB database. Intersected the target genes of AR-CR and CG, then protein-protein interaction(PPI) network was constructed by STRING website. The overlapped genes were subjected to gene ontology༈GO༉enrichment and Kyoto encyclopedia of genes and genomes༈KEGG༉pathway enrichment analyses by David. Results 45 intersection genes were obtained, and there were 40 targets in the PPI network for protein interaction, the kernel targets with Degree ≥ 10 included AKT1, TNF, JUN, MAPK3, MAPK8 and MAPK1. The Go enrichment analysis was mainly related to protein binding, enzyme binding, protein homodimerization activity, etc. The KEGG pathway enrichment analyses mainly involved the Pathways in cancer, TNF signaling pathway, Apoptosis, and VEGF signaling pathway. Conclusion AR-CR might delayed, blocked or reversed the atrophy, intestinal metaplasia, dysplasia and canceration of gastric mucosa by targeting key proteins and signal pathways,achieved the effect of the treatment of CG.


Sign in / Sign up

Export Citation Format

Share Document